Cell death is the central reaction of cells to injury in human disease. Ischemia and chemical toxins are two of the important causes of cell death, and the present application is concerned with the biochemical mechanisms underlying their action on cells. In general the specific aims encompass analysis of the mechanisms underlying membrane injury and the functional consequences of such injury in 3 different forms of experimental liver cell death: (l) a toxic alkylating chemical, methyl methane sulfonate, (2) galactosamine-induced liver cell necrosis, and (3) irreversible, ischemic cell injury. In each case the specific aim will be to relate a particular kind of membrane alteration to changes in intracellular calcium homeostasis known to occur in each situation and hypothesized to be causally related to the loss of viability.